The research analyzes the way in which neurons of the mature mammalian central nervous system respond to brain lesions, by analyzing one situation in which brain lesions induce a dramatic reorganization of surviving circuitry. Specifically, the reinnervation of the dentate gyrus of the hippocampal formation is analyzed following unilateral destruction of its major source of synaptic input (from the entorhinal cortex). Following such brain lesions, among other changes, the denervated dentate gyrus is reinnervated by connections from the surviving contralateral entorhinal area. The specific questions analyzed include 1) What is the nature of the changes which occur in surviving connections following the lesions? How do projections from the contralateral entorhinal area accomplish the task of reinnervating the denervated cells? 2) What cytological and morphological changes occur in cells which are sprouting, and does the proliferation of synaptic connections require increased synthesis of RNA and protein by the sprouting cells? 3) What are the physiological consequences of the changes in circuitry which result from the lesions? How are the cells which receive the lesion-induced inputs affected, and in what ways are the lesion-induced connections similar or dissimilar from the normal circuitry which had been destroyed. 4) Does this sort of reorganization of brain circuitry occur following lesions in a variety of mammals (for example, the cat) or is it unique to less phylogenetically advanced mammals such as the rat? It is hoped that these investigations of one situation in which neurons do grow new connections following brain lesions might provide some insight into the reasons why neurons of the mammalian central nervous system are typically incapable of regeneration following damage.